BRAINFUL (BRAIN Tumor Focused Ultrasound-enabled Liquid Biopsy) Trial

NCT04940507 | Active Not Recruiting DMC

• 2 other identifiers: 20-6243707126
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Accessing brain tumor material for pathological diagnosis requires invasive procedures that carry risk to patients including brain hemorrhages and death. Liquid biopsies are emerging non-invasive alternatives to direct tumour biopsies but the abundance of circulating tumor DNA (ctDNA) is relatively low and this limits our ability to accurately make the molecular diagnosis of brain tumors. We have recently shown promising results that suggest that the analysis of blood samples can distinguish brain tumor types. We now want to couple liquid biopsies with high intensity focused ultrasound (HIFU) to enhance the release of tumor DNA into the circulation and increase the sensitivity/and specificity of liquid biopsies for brain tumors. The aim of this project is to build on our preliminary findings and investigate the the time dependent changes associated with HIFU of a tumor to see if it improves accuracy of diagnosis and specifically molecular subtyping of tumors based on peripheral blood and cerebrospinal fluid (CSF) circulating tumor derived markers following HIFU.

Conditions

Brain Neoplasms; Liquid Biopsy

Keywords

High-Intensity Focused Ultrasound Ablation

Outcome Measures

Primary Outcomes (1)

• Blood and CSF levels of the circulating free DNA

  Difference in concentration of cfDNA between the blood and CSF samples acquired before and after MRgFUS

  Pre-MRgFUS: Within 1 hour; Post-MRgFUS: Within 1 hour, between 3-4 hours; Pre-surgery: Within 1 hour; Post-surgery:Within 1 hour, between 16-24 hours

Secondary Outcomes (4)

• The optimal time-point of liquid biopsy acquisition

  Pre-MRgFUS: Within 1 hour; Post-MRgFUS: Within 1 hour, between 3-4 hours; Pre-surgery: Within 1 hour; Post-surgery:Within 1 hour, between 16-24 hours

• Safety (procedure-related complications)

  Post-MRgFUS: Within 1 hour, between 3-4 hours; Pre-surgery: Within 1 hour; Post-surgery: Within 1 hour, between 16-24 hours and 1 month

• Epigenomic analysis

  Pre-MRgFUS: Within 1 hour; Post-MRgFUS: Within 1 hour, between 3-4 hours; Pre-surgery: Within 1 hour; Post-surgery:Within 1 hour, between 16-24 hours

• Genomic analysis

  Pre-MRgFUS: Within 1 hour; Post-MRgFUS: Within 1 hour, between 3-4 hours; Pre-surgery: Within 1 hour; Post-surgery:Within 1 hour, between 16-24 hours

Study Arms (2)

Tumor cohort

EXPERIMENTAL

Intervention 1: Participants will undergo a partial tumor ablation with MRgFUS using ExAblate Neuro 4000 device (InSightec Ltd, Tirat Carmel, Israel). Blood and CSF samples will be drawn on several timepoints before and after the procedure. Intervention 2: Participants will undergo a standard of care tumor biopsy/excision one day after the "Intervention 1". Blood samples will be drawn on several timepoints before and after the procedure.

Procedure: Magnetic Resonance Guided Focused Ultrasound Tumor Ablation and Liquid Biopsy Acquisition

Essential tremor cohort

OTHER

To identify the levels of circulating free DNA release after MRgFUS procedure in non-tumoral patients and to check whether the MRgFUS procedure induce tumoral mutations itself, we will draw blood samples from essential tremor patients before and after standard of care MRgFUS thalamotomy procedure.

Procedure: Magnetic Resonance Guided Focused Ultrasound Thalamotomy

Interventions

Magnetic Resonance Guided Focused Ultrasound Tumor Ablation and Liquid Biopsy Acquisition PROCEDURE

Partial ablation of tumor using ExAblate Neuro 4000 device (InSightec Ltd, Tirat Carmel, Israel) and blood and CSF draws for liquid biopsy

Also known as: Neurosurgical Tumor Biopsy/Excision

Tumor cohort

Magnetic Resonance Guided Focused Ultrasound Thalamotomy PROCEDURE

Ablation of VIM nucleus of thalamus with MRgFUS using ExAblate Neuro 4000 Device (InSightec Ltd, Tirat Carmel, Israel) and blood draws.

Essential tremor cohort

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• New MRI-diagnosed intracranial lesions that are suitable to biopsy surgically
• The lesion to be treated is clearly defined and can be well distinguished from surrounding brain tissue.
• Male or female aged 18 years or older
• Capable of providing informed consent and complying with study procedures, including tolerability in the supine position and MRI examination without significant claustrophobia, and acceptance of surgery (open or stereotactic) after HIFU treatment.
• Able to communicate during the ExAblate® MRgFUS procedure.
• Karnofsky rating 70-100

You may not qualify if:

• If region of treatment locates in \< 1.0 cm from the inner table of the skull, on skull base or in the posterior fossa
• Presence of hydrocephalus, severe vomiting, intractable headache or decreased level of consciousness due to increased intracranial pressure
• Unable to complete high-density CT and MRI studies of the head at the any other MRI contraindication, such as:
• Large body habitus and not fitting comfortably into the scanner
• Difficulty lying supine and still for up to 2 in the MRI unit or significant claustrophobia
• MRI findings:
• Active infection/inflammation
• Acute or chronic brain haemorrhages
• Moderate/severe brain edema or midline shift \>15 mm
• Clips or other metallic implanted objects in the skull or the brain, except shunts
• Significant cardiac disease or unstable hemodynamic status.
• On medications that increase the bleeding risk, specifically: a) aspirin or another antiplatelet medication (clopidogrel, prasugrel, ticlopidine, abciximab) for the last 7 days prior to treatment; b) oral, subcutaneous or intravenous anticoagulant medications, such as oral vitamin K inhibitors for the last 7 days, non-vitamin K inhibitor oral anticoagulant (dabigatran, apixaban, rivaroxaban) for the last 72 hours, and intravenous or subcutaneous heparin-derived compounds for the last 48 hours
• Abnormal coagulation profile, specifically: platelet \<100,000/μl, Prothrombin Time \>14 seconds, activated partial thromboplastin time (aPTT) \>36 seconds, and INR \> 1.3
• Unqualified fit for the anaesthesia by an anesthesiologist assessment, ASA IV-V.
• Currently in a clinical trial involving an investigational product or non-approved use of a drug or device.

Sponsors & Collaborators

• University Health Network, Toronto: lead
• Canadian Cancer Society (CCS): collaborator
• Brain Canada: collaborator

Study Sites (1)

Toronto Western Hospital, University Health Network

Toronto, Ontario, M5T 2S8, Canada

Location

MeSH Terms

Conditions

Brain Neoplasms

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Officials

• Andres M. Lozano, MD, PhD

  University of Toronto

  PRINCIPAL INVESTIGATOR

• Gelareh Zadeh, MD, PhD

  University of Toronto

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 17, 2021
• First Posted: June 25, 2021
• Study Start: June 10, 2021
• Primary Completion: December 31, 2025
• Study Completion (Estimated): December 31, 2026
• Last Updated: June 22, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)